Submissions for variant NM_024312.5(GNPTAB):c.204-15G>T

gnomAD frequency: 0.01423  dbSNP: rs10860787

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000328472	SCV000375449	benign	Mucolipidosis type II	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000380692	SCV000375450	benign	Pseudo-Hurler polydystrophy	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587904	SCV000699477	benign	not provided	2016-10-10	criteria provided, single submitter	clinical testing	Variant summary: The GNPTAB c.204-15G>T variant involves the alteration of a non-conserved intronic nucleotide. Mutation taster predicts a benign outcome for this variant along with 5/5 splice prediction tools predict no significant impact on splicing. This variant was found in 5864/121394 control chromosomes (675 homozygotes), predominantly observed in the East Asian subpopulation at a frequency of 0.3188339 (2756/8644). This frequency greatly exceeds the estimated maximal expected allele frequency of a pathogenic GNPTAB variant (0.0022361), indicating this is a benign polymorphism found primarily in the populations of East Asian origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. One reputable clinical lab has classified the variant as benign. Taken together, this variant is classified as benign.
GeneDx	RCV000587904	SCV000975317	benign	not provided	2018-06-19	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001518439	SCV001727130	benign	Mucolipidosis type II; Pseudo-Hurler polydystrophy	2025-01-28	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000328472	SCV001749159	benign	Mucolipidosis type II	2021-07-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000380692	SCV001749160	benign	Pseudo-Hurler polydystrophy	2021-07-01	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000587904	SCV005235019	benign	not provided		criteria provided, single submitter	not provided
Mayo Clinic Laboratories, Mayo Clinic	RCV000587904	SCV000800959	benign	not provided	2017-12-06	no assertion criteria provided	clinical testing